Melatonin
TL;DR
Melatonin is a pineal hormone that signals “time to sleep” via the suprachiasmatic nucleus — it is a circadian entrainment signal, not a hypnotic. At 0.5–5 mg it reduces sleep-onset latency by ~7–17 min; jet lag benefit is well-established (NNT=2, Cochrane-grade). 0.5 mg is nearly as effective as 5 mg for sleep onset. High-dose anti-aging and GH claims are unsubstantiated at supplement doses. Most commercial products are off-label dose; 26% contain undisclosed serotonin.
Why it matters for Vitals
Melatonin is the most accessible sleep-onset intervention with a clear evidence base. Vitals coaching needs to distinguish:
- what melatonin actually does (sleep-onset timing) vs. what it doesn’t do (sleep quality amplification, GH boost, anti-aging)
- physiological replacement (0.5 mg) vs. supraphysiological dosing (3–5 mg+)
- timing sensitivity — taken too late it can cause phase delay; taken 3h before bedtime it outperforms the common 30-min approach
Product sourcing is a real-world risk: 71% of commercial melatonin fails label within 10%, and 26% contain undisclosed serotonin — relevant for users on SSRIs or with cardiac concerns.
Key facts
| Parameter | Value |
|---|---|
| Mechanism | Circadian signal via SCN; not a direct sedative |
| Sleep onset (adults, 0.5–5 mg) | ~7–17 min SOL reduction; modest, consistent |
| Jet lag (≥5 time zones) | NNT=2; Cochrane-grade evidence |
| Pediatric sleep onset | 37 min earlier onset, 23 min more sleep |
| Elderly ≥55 | 2 mg PR-melatonin (Circadin®); EU-approved |
| Sleep architecture | No meaningful change at physiological doses (0.3–1 mg) |
| Recommended dose | 0.5–4 mg; 0.5 mg nearly as effective as 5 mg |
| Optimal timing | 30 min–3 hours before desired bedtime; 3h before outperforms 30 min |
| Bioavailability | 9–33%; T½ ~45 min (immediate-release) |
| Metabolism | CYP1A2 → 6-hydroxymelatonin → 6-sulfatoxymelatonin (inactive) |
| Long-term safety | No tolerance, withdrawal, or rebound up to 12 months |
| High-dose (>10 mg) | No greater efficacy; more adverse events; GH/anti-aging claims DEBUNKED |
Mechanism summary
Melatonin is synthesized from tryptophan in the pineal gland and released in response to darkness, peaking during the biological night (~02:00–04:00). Its primary role is to signal circadian phase to the SCN, not to directly induce sleep. Sleepiness is a downstream consequence of SCN signaling.
Phase-response curve:
- Late afternoon/early evening → phase advance (earlier sleep)
- Bedtime or after sleep onset → minimal phase effect
- Morning → phase delay (later sleep) — counterproductive
Key distinction from hypnotics: Melatonin does not amplify sleep depth or quality at physiological replacement doses. Z-drugs and melatonin act on fundamentally different pathways.
See Circadian Biology for the broader SCN/peripheral clock system.
What the current evidence suggests
Supported
- Sleep onset (adults): ~7–17 min SOL reduction at 0.5–5 mg. Effect is modest, heterogeneous by population and insomnia subtype. 4 mg at 3h before bedtime outperforms 2 mg at 30 min (Kaufmann 2024, PMID 38888087).
- Sleep onset (children/adolescents): 37 min earlier onset, 23 min more sleep; strongest evidence in ADHD/ASD populations.
- Jet lag (≥5 zones): NNT=2; eastward travel benefits most; dose 0.5–5 mg at destination bedtime.
- Elderly ≥55, primary insomnia: 2 mg controlled-release (Circadin®) approved in EU/Australia.
- Low vs. standard dose: 0.5 mg nearly as effective as 5 mg for sleep latency.
- Long-term safety: No tolerance, withdrawal, or rebound up to 12 months.
Contested / gaps
- Sleep architecture: High doses (≥5 mg) may increase REM; low doses do not alter N1/N3/REM proportions. Sleep architecture is not meaningfully improved at physiological doses.
- Shift work sleep: Modest sleep length improvement; no global recovery.
- HPA axis / cortisol: No suppression in waking young men; population-specific data lacking.
- Anti-inflammatory: Strong preclinical; clinical trials inconclusive at supplement doses.
Debunked at supplement doses
- GH boost: Human pharmacological data uses gram doses; clinically irrelevant to supplementation.
- Anti-aging: No human evidence at supplement doses.
Likely wearable / Vitals relevance
See Melatonin Sleep Biometrics and Melatonin Detection Model for full detail.
Summary: Consumer wearables cannot directly detect melatonin ingestion. Any biometric inference (improved SOL, elevated overnight HRV, reduced resting heart rate) is proxy-only and not individually validated for melatonin. These signals are confounded by baseline variation, device noise, and other behavioral factors.
For coaching: the most defensible wearable signal is sleep-onset latency improvement — and even this is within device error margins for most consumers.
Risks and uncertainty
| Risk | Detail |
|---|---|
| Product contamination | 71% off-label dose; 26% contain undisclosed serotonin |
| Fluvoxamine interaction | Severe — 17-fold AUC increase via CYP1A2 inhibition |
| Pregnancy | Not recommended |
| Seizure disorders | Contested — some EEG abnormality reports |
| Diabetes | 3-month use reduced insulin sensitivity in T2D (PMID 35619221) |
| Anticoagulants | Theoretical platelet inhibition risk |
| Morning use | Can cause phase delay — actively counterproductive |
Contamination guardrail: Recommend USP-verified or third-party tested products only. Liquid/gummy formulations carry higher stability and content variance risk.
Best stack context
Melatonin pairs with:
- Magnesium Glycinate — complementary sleep-onset pathways; both are mild and physiologically rational at low doses
- L-Theanine — calming without sedation; can combine with melatonin for sleep-onset stack
- Sleep Optimization — melatonin is one lever in a broader sleep hygiene protocol
- Light management — melatonin efficacy depends on dim-light environment; pair with Circadian Biology principles
Not a stack candidate with:
- High-dose GH secretagogues (GH claim is debunked)
- Anti-aging stacks (unsubstantiated mechanism)
What stays inside this hub
The following are kept inside this hub rather than split into separate notes:
- GH mechanism (debunked at supplement doses — not reusable)
- Anti-inflammatory mechanism (preclinical only, not clinically actionable)
- Specific drug interaction details (available inline)
- Product sourcing detail (available inline)
Related notes
In vault:
- Circadian Biology — SCN master clock, peripheral clocks, zeitgebers
- Sleep architecture — sleep stage patterns; melatonin does not meaningfully alter at physiological doses
- HRV — HRV may increase with melatonin (lab ECG evidence); consumer wearable validation absent
- Melatonin Beyond Sleep — melatonin as a timing and systems hormone (oncostatic, immune, metabolic signaling)
- Melatonin Oncostatic Signaling — anti-angiogenesis, NK cell activation, p53/BMAL1 regulation
- Magnesium Glycinate — complementary sleep-onset stack
- L-Theanine — complementary calming stack
- Sleep Optimization — broader sleep coaching protocol
- Melatonin Sleep Biometrics — what wearable metrics melatonin changes and how reliably
- Melatonin Detection Model — wearable inference logic and its limits
Implementation: